- Email: [email protected]
24. Clinical usefulness of biological markers in breast cancer
166
The Breast
3 were (+) and 7 were (++). All hyperplastic lesions showed immunostaining: 3 cases were (+) and 1 was (++). In the normal breast tissues 10 cases showed immunostaining: 2 were (+) and 8 were (++). The results were compared to ER status, lymph nodes status,and ploidy status. While no correlation was found regarding bcl-2 immunostained tumours and the corresponding lymph node status, we found that the majority of tumours showing bcl-2 immunostaining were ER-positive (17/19), and diploid (1609).
22. Significance of MeHPLA-ase
3 showing the maximum and MDA-MD-231 the minimum level. DNA from 68 primary human breast cancer biopsies was analysed by Southern blot. In no case evidence of any rearrangement of the RON locus was seen. EcoRI restriction identified a RON dimorphism (9 tumours and ZR-75.1 cells). Tumours showing the rare RON EcoRI allele were frequently positive for ~53 and
erbB-2. Our preliminary results confirm that the RON gene has a role in the physiology of breast cancer cells; immunoblotting analysis of the RON protein expression in tumour biopsies is under way.
in breast cancer
F G Serra, A Carbone, D Terribile, A Picciocchi, R Bellantone, R Masetti, G Scambia, A Rinelli, M Piantelli and F 0 Ranelletti
Universitir di Chieti, Ztalia In human target tissues two oestrogen-binding macromolecules (ER, estrogen receptor, and type II EBS, oestrogen binding sites) have been demonstrated. ER, which binds to oestrogen, acts in target organs stimulating cell proliferation, whereas type II EBS, which interact with oestrogen and with a specific endogenous ligand, has a growth inhibitory action. The ligand has been identified as methyl-p-hydroxyphenyl-lactate (MeHPLA). MeHPLA is demethylated to HPLA by MeHPLA esterase. HPLA is inactive in terms of cell growth inhibition as compared to MeHPLA. It is possible to suppose that the MeHPLA-ase may have an important role in neoplastic growth by inhibiting the antiproliferative action of type II EBS. We examined endotumoral levels of MeHPLA-ase, ER, PgR and the number of involved lymph nodes. An inverse correlation was found between MeHPLA-ase activity and ER and PgR levels (n = 49, P = 0.034 and n = 48, P = 0.04, respectively), while a direct relationship was demonstrated with the number of metastatic lymph nodes (n = 37, P = 0.007). Thus, high levels of MeHPLA-ase seem to be associated to unfavourable prognostic markers in breast cancer.
23. Structure and expression of the RON tyrosine kinase receptor gene in human breast cancer S Marchib, M Giai, P Sismondi and M De Bortoli The recently discovered RON gene codes for a tyrosine kinase receptor structurally related to the MEUhepatocyte growth factor receptor and is the receptor for the Macrophage Stimulating Protein (MSP) (Gardino et al EMBO J., 13: 3524, 1994). The interest in this new receptor for breast cancer is twice: fist, MSP has proven to be mitogenic for breast cancer cells in culture; second, the HGF/Met system has been implicated in morphogenesis also for mammary cells (Rosen et al J. Cell. Biol., 127: 1783, 1994). Therefore, we have undetaken a study on the genomic structure and expression of RON in breast cancer. First, RON was studied in breast cancer cell lines. DNA from MCF-7, ZR-75.1, T-47D, MDA-MB-231, SKBR-3 and BT-474 cells was restricted with BamHI and EcoRI and subjected to Southern blot analysis with a full-length RON cDNA. Hybridization to both a P-globin probe and a MSP cDNA (which also maps to chromosome 3~21) was done as control. Immunoblotting analysis of the 150 kd RON protein was performed after immunoprecipitation of lysates of the same cell lines. Southern blot analysis gave no indication of genomic rearrangement in any of the cell lines examined. Conversely, RON protein was expressed in all the cell lines at variable level, SKBR-
24. Clinical usefulness of biological markers in breast cancer P Querzoli, G Albonico, S Ferretti, R Rinaldi, M Indelli and I Nenci
Universitd di Ferrara, Italy Among the techniques available, immunohistochemistry (MC) can define breast cancer biological phenotypes. We currently use IHC to assess several biological markers including oestrogen (ER) and progesterone (PR) receptors, proliferation index (PI), p53 and c-erbB2/Neu overexpression on a series of 2036 primary intiltrating breast cancer. Clinical usefulness of biological assessment was evaluated in 461 patients (median follow up of 71.6 months); patients median age was 58.4 years; 40% were premenopausal; 49.6% were node-negative (N-). Seventy-eight percent of tumours were ductal type, 14% lobular, 8% special type; 58.2% of tumours were pT1. Seventy-three percent and 51.8% of tumours were ERICA and PR-ICA positive; 33.7% had a high PI, 35.4% and 27.7% overexpressed Neu and p53 respectively. The results about the prognostic power (RF& OS) of the different pathological and biological parameters, evaluated in univariate (461 cases) and multivariate (241 cases) analysis are the follows: in N- patients, PI and Neu showed the higher prognostic power for both univariate (RFI e OS P < 0.001 for PI; RFI P = 0.010 and OS = 0.009 for Neu) and multivariate (RFI P = 0.019 and OS = 0.026 for PI; RFI P = 0.033 and OS P = 0.022 for Neu) analysis. In N+ patients, ER (RFI P = 0.002 and OS P
25. Breast complaints and age as indicators of breast disease F Lumachi, G Favia, P Boccagni, D F D’Amico University of Padova, Ztaly Breast complaints seem to be related to the age of the patients, than to their pathology and in women over 55 years breast cancer is more frequent. We have looked for a definite correlation between patients’ sign and symptoms, age and risk of benign or malignant breast diseases. From 1983 to 1994 we observed 2356 consecutive patients with breast disease who were asked to complete a questionnaire before clinical examination. Only 242 (10.3%) patients had already a mammography or breast ultrasonography. Patients were assigned by age to three groups: group
The Breast
3 were (+) and 7 were (++). All hyperplastic lesions showed immunostaining: 3 cases were (+) and 1 was (++). In the normal breast tissues 10 cases showed immunostaining: 2 were (+) and 8 were (++). The results were compared to ER status, lymph nodes status,and ploidy status. While no correlation was found regarding bcl-2 immunostained tumours and the corresponding lymph node status, we found that the majority of tumours showing bcl-2 immunostaining were ER-positive (17/19), and diploid (1609).
22. Significance of MeHPLA-ase
3 showing the maximum and MDA-MD-231 the minimum level. DNA from 68 primary human breast cancer biopsies was analysed by Southern blot. In no case evidence of any rearrangement of the RON locus was seen. EcoRI restriction identified a RON dimorphism (9 tumours and ZR-75.1 cells). Tumours showing the rare RON EcoRI allele were frequently positive for ~53 and
erbB-2. Our preliminary results confirm that the RON gene has a role in the physiology of breast cancer cells; immunoblotting analysis of the RON protein expression in tumour biopsies is under way.
in breast cancer
F G Serra, A Carbone, D Terribile, A Picciocchi, R Bellantone, R Masetti, G Scambia, A Rinelli, M Piantelli and F 0 Ranelletti
Universitir di Chieti, Ztalia In human target tissues two oestrogen-binding macromolecules (ER, estrogen receptor, and type II EBS, oestrogen binding sites) have been demonstrated. ER, which binds to oestrogen, acts in target organs stimulating cell proliferation, whereas type II EBS, which interact with oestrogen and with a specific endogenous ligand, has a growth inhibitory action. The ligand has been identified as methyl-p-hydroxyphenyl-lactate (MeHPLA). MeHPLA is demethylated to HPLA by MeHPLA esterase. HPLA is inactive in terms of cell growth inhibition as compared to MeHPLA. It is possible to suppose that the MeHPLA-ase may have an important role in neoplastic growth by inhibiting the antiproliferative action of type II EBS. We examined endotumoral levels of MeHPLA-ase, ER, PgR and the number of involved lymph nodes. An inverse correlation was found between MeHPLA-ase activity and ER and PgR levels (n = 49, P = 0.034 and n = 48, P = 0.04, respectively), while a direct relationship was demonstrated with the number of metastatic lymph nodes (n = 37, P = 0.007). Thus, high levels of MeHPLA-ase seem to be associated to unfavourable prognostic markers in breast cancer.
23. Structure and expression of the RON tyrosine kinase receptor gene in human breast cancer S Marchib, M Giai, P Sismondi and M De Bortoli The recently discovered RON gene codes for a tyrosine kinase receptor structurally related to the MEUhepatocyte growth factor receptor and is the receptor for the Macrophage Stimulating Protein (MSP) (Gardino et al EMBO J., 13: 3524, 1994). The interest in this new receptor for breast cancer is twice: fist, MSP has proven to be mitogenic for breast cancer cells in culture; second, the HGF/Met system has been implicated in morphogenesis also for mammary cells (Rosen et al J. Cell. Biol., 127: 1783, 1994). Therefore, we have undetaken a study on the genomic structure and expression of RON in breast cancer. First, RON was studied in breast cancer cell lines. DNA from MCF-7, ZR-75.1, T-47D, MDA-MB-231, SKBR-3 and BT-474 cells was restricted with BamHI and EcoRI and subjected to Southern blot analysis with a full-length RON cDNA. Hybridization to both a P-globin probe and a MSP cDNA (which also maps to chromosome 3~21) was done as control. Immunoblotting analysis of the 150 kd RON protein was performed after immunoprecipitation of lysates of the same cell lines. Southern blot analysis gave no indication of genomic rearrangement in any of the cell lines examined. Conversely, RON protein was expressed in all the cell lines at variable level, SKBR-
24. Clinical usefulness of biological markers in breast cancer P Querzoli, G Albonico, S Ferretti, R Rinaldi, M Indelli and I Nenci
Universitd di Ferrara, Italy Among the techniques available, immunohistochemistry (MC) can define breast cancer biological phenotypes. We currently use IHC to assess several biological markers including oestrogen (ER) and progesterone (PR) receptors, proliferation index (PI), p53 and c-erbB2/Neu overexpression on a series of 2036 primary intiltrating breast cancer. Clinical usefulness of biological assessment was evaluated in 461 patients (median follow up of 71.6 months); patients median age was 58.4 years; 40% were premenopausal; 49.6% were node-negative (N-). Seventy-eight percent of tumours were ductal type, 14% lobular, 8% special type; 58.2% of tumours were pT1. Seventy-three percent and 51.8% of tumours were ERICA and PR-ICA positive; 33.7% had a high PI, 35.4% and 27.7% overexpressed Neu and p53 respectively. The results about the prognostic power (RF& OS) of the different pathological and biological parameters, evaluated in univariate (461 cases) and multivariate (241 cases) analysis are the follows: in N- patients, PI and Neu showed the higher prognostic power for both univariate (RFI e OS P < 0.001 for PI; RFI P = 0.010 and OS = 0.009 for Neu) and multivariate (RFI P = 0.019 and OS = 0.026 for PI; RFI P = 0.033 and OS P = 0.022 for Neu) analysis. In N+ patients, ER (RFI P = 0.002 and OS P
25. Breast complaints and age as indicators of breast disease F Lumachi, G Favia, P Boccagni, D F D’Amico University of Padova, Ztaly Breast complaints seem to be related to the age of the patients, than to their pathology and in women over 55 years breast cancer is more frequent. We have looked for a definite correlation between patients’ sign and symptoms, age and risk of benign or malignant breast diseases. From 1983 to 1994 we observed 2356 consecutive patients with breast disease who were asked to complete a questionnaire before clinical examination. Only 242 (10.3%) patients had already a mammography or breast ultrasonography. Patients were assigned by age to three groups: group